Correlation of ERCC1 expression in peripheral blood lymphocytes with outcomes of patients with gastric cancer treated with oxaliplatin-based adjuvant chemotherapy.

Excision repair cross-complementing gene-1 (ERCC1) is a key regulatory enzyme whose expression patterns in tumor tissues are associated with survival in gastric cancer. The present study aimed to evaluate the effects of ERCC1 expression in peripheral blood lymphocytes (PBLs) on the outcome of patients with gastric cancer treated with oxaliplatin-based adjuvant chemotherapy. Tumor and PBL samples from 48 patients treated with adjuvant oxaliplatin-based chemotherapy for gastric cancer were analyzed. Immunohistochemistry was used to assess the expression of ERCC1. After a median follow-up of 18.5 months, the median disease-free survival (DFS) and overall survival (OS) were 12 and 20 months, respectively. Expression of ERCC1 was found in 72.9% (35/48), 56.3% (27/48), and 10.0% (2/20) of tumor tissues, PBLs from gastric cancer patients, and PBLs from controls, respectively. A significant positive correlation between ERCC1 expression in PBL and cancer tissue was found (χ(2) = 12.098, P = 0.001, Pearson contingency coefficient = 0.502). Patients with negative expression of ERCC1 in tumor tissues had a significantly longer median DFS and median OS compared to patients with positive expression of ERCC1 (median DFS, 18 vs 10 months, P = 0.006; median OS, 30 vs 17 months, P = 0.012). In PBLs, high expression of ERCC1 was associated with decreased DFS (9 vs 18 months, P = 0.032), but not OS (16 vs 24 months, P = 0.057). Patients with gastric cancer exhibiting negative expression of ERCC1 are more likely to benefit from oxaliplatin-based adjuvant chemotherapy.

Clinical retrospective analysis of cases with multiple primary malignant neoplasms.

The etiological factors, clinical characteristics, diagnosis, treatment strategies, and prognosis of multiple primary malignant neoplasms (MPMNs) were investigated in order to improve its diagnosis and therapy. Clinical data of 170 patients with MPMN who were admitted to the Oncology Department of the First Affiliated Hospital of Anhui Medical University from January 2004 to April 2010 were collected and analyzed retrospectively. The overall incidence of MPMNs was 2.25%. There were 167 cases with duplex primary cancers, 2 cases with triple primary cancers, 1 case with quadruple primary cancer, 46 synchronous MPMNs (SMPMNs), and 124 metachronous MPMNs (MMPMNs). There were 344 malignant neoplasms in the 170 MPMN patients, of which 161 were in the alimentary system, 48 in the respiratory system, 63 in mammary glands, 30 in the genital system, 7 in the urinary system, 23 in the head and neck, and the other 12 were in the brain, hematological system, and soft tissue. There were 22 cases of bilateral primary breast cancer and 41 cases of digestive MPMN. With a median survival time of 24 months, the 1-, 3-, and 5-year cumulative survival rates in the 170 patients were 68.8, 39.1, and 25.2%, respectively. The most common locations of MPMN were the alimentary system, mammary gland, and respiratory system. MPMN usually occurred in distinct organs of identical systems, conjugate organs, or identical organs. The survival rate of SMPMN was similar to that of MMPMN. There were differences in principles of treatment and diagnosis between MPMN and metastasis or recurrent cancers.

A nanomaterial-based breath test for distinguishing gastric cancer from benign gastric conditions.

BACKGROUND: Upper digestive endoscopy with biopsy and histopathological evaluation of the biopsy material is the standard method for diagnosing gastric cancer (GC). However, this procedure may not be widely available for screening in the developing world, whereas in developed countries endoscopy is frequently used without major clinical gain. There is a high demand for a simple and non-invasive test for selecting the individuals at increased risk that should undergo the endoscopic examination. Here, we studied the feasibility of a nanomaterial-based breath test for identifying GC among patients with gastric complaints. METHODS: Alveolar exhaled breath samples from 130 patients with gastric complaints (37 GC/32 ulcers / 61 less severe conditions) that underwent endoscopy/biopsy were analyzed using nanomaterial-based sensors. Predictive models were built employing discriminant factor analysis (DFA) pattern recognition, and their stability against possible confounding factors (alcohol/tobacco consumption; Helicobacter pylori) was tested. Classification success was determined (i) using leave-one-out cross-validation and (ii) by randomly blinding 25% of the samples as a validation set. Complementary chemical analysis of the breath samples was performed using gas chromatography coupled with mass spectrometry. RESULTS: Three DFA models were developed that achieved excellent discrimination between the subpopulations: (i) GC vs benign gastric conditions, among all the patients (89% sensitivity; 90% specificity); (ii) early stage GC (I and II) vs late stage (III and IV), among GC patients (89% sensitivity; 94% specificity); and (iii) ulcer vs less severe, among benign conditions (84% sensitivity; 87% specificity). The models were insensitive against the tested confounding factors. Chemical analysis found that five volatile organic compounds (2-propenenitrile, 2-butoxy-ethanol, furfural, 6-methyl-5-hepten-2-one and isoprene) were significantly elevated in patients with GC and/or peptic ulcer, as compared with less severe gastric conditions. The concentrations both in the room air and in the breath samples were in the single p.p.b.v range, except in the case of isoprene. CONCLUSION: The preliminary results of this pilot study could open a new and promising avenue to diagnose GC and distinguish it from other gastric diseases. It should be noted that the applied methods are complementary and the potential marker compounds identified by gas-chromatography/mass spectrometry are not necessarily responsible for the differences in the sensor responses. Although this pilot study does not allow drawing far-reaching conclusions, the encouraging preliminary results presented here have initiated a large multicentre clinical trial to confirm the observed patterns for GC and benign gastric conditions.

Multidrug resistance in leukemic cell line K562/A02 induced by doxorubicin.

AIM: To study the mechanism of the development of multidrug resistance in leukemic cells. METHODS: A human leukemic cell line K562/A02 was established by stepwise increase of concentrations of doxorubicin (Dox) in medium. P-glycoprotein was detected by immunohistochemistry assay. The mdr1 gene expression was measured by RT-PCR. The amplification of mdr1 gene in its genome, and DNA topisomerase II (Top II) gene expression were determined by dot-blot hybridization. RESULTS: K562/A02 was highly cross-resistant to vincristine (VCR), homoharringtonin (HHT), amsacrine (m-AMSA), daunorubicin (Dau) and etoposide (VP-16), slightly to cytosine arabinoside (Ara-C), but not cisplatin (Cis), methotrexate (MTX) and fluorouracil (5-FU), showing a typical phenotype of MDR. Intracellular accumulation of Dau in K562/A02 was 33% as high as that in K562. P-glycoprotein P-170 was positive. In K562/A02, the mdr1 gene did not amplify, the mdr1 mRNA level was markedly higher, the Top II mRNA level was lower, and glutathione-S-transferase (GST) activity was higher than in K562. CONCLUSION: mdr1 mRNA was overexpression and thus the encoded P-170 was responsible for MDR in K562/A02 while Top II or GST may play a role in MDR.

[Multiple primary lung cancer].

From November 1957 to June 1984, 30 patients with multiple primary lung cancer were diagnosed, basing on clinical features, diagnostic means, histologic type, treatment and prognosis. Out of 3,815 cases of resected primary lung cancer, the incidence of multiple primary cancer was 0.8%. There were 10 synchronous and 20 metachronous cases. There were 17 unilateral, only 1 simultaneous bilateral and 12 contralateral after resection of cancer in the opposite lung. Four of the 10 synchronous cases were definitely diagnosed preoperatively. Among the 20 metachronous cases, 9 were definitely diagnosed as a second primary lesion and the other 11 were proved by thoracotomy. Pathologically, 19 had identical types (15 squamous cell and 4 adenocarcinoma) but 11 had double types (9 squamous cell + adenocarcinoma, 2 squamous cell + anaplastic). The average survival of these 30 patients was 27.1 months, that in the synchronous group was 29 months and that in the metachronous group was 26.2 months. The 5 year survival rate of the synchronous cases was 35%, that of the metachronous cases was 42%. The clinicopathological criteria of multiple primary lung cancer, early diagnostic and operative procedure are also discussed.